Abstract 1786: Effect of DUSP2 on pancreatic cancer lymphatic dissemination
| Autor: | Shaw-Jenq Tsai, Chu-An Wang, I-Heng Chang |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Cancer Research. 79:1786-1786 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2019-1786 |
| Popis: | More than 90% of pancreatic cancers are originated from the exocrine ducts of the pancreas, which is called pancreatic ductal adenocarcinoma (PDAC). PDAC is notorious for the high early metastatic rate and low 5-year survival rate. Vascular endothelial growth factor C (VEGF-C), a member of the VEGF family, was first identified as the master lymphangiogenic factor in embryonic development. Overexpression of VEGF-C in cancers has been tightly linked to lymphangiogenesis and is highly associated with lymphatic invasion and metastasis; however, the underlying mechanism responsible for VEGF-C overexpression remains largely unknown. Constitutive activation of MAPK pathway was characterized as feature of pancreatic cancer. In genetic mouse model of pancreatic cancer, MAPK signaling is required to initiate and maintain the pancreatic intraepithelial neoplasia lesions. In normal cells, MAPKs mediated signaling is crucial to various cell functions and the activation can be balanced by the action of dual specificity phosphatases (DUSPs). Previously, we have demonstrated that hypoxia can suppress DUSP2 by which mediates tumor malignancy and drug resistance. Herein, we further identify that DUSP2 is a master regulator in controlling lymphangiogenesis and early lymphovascular invasion of PDAC. Expression of DUSP2 is silenced in PDAC, which contributes to aberrant production of VEGF-C. VEGF-C expression is controlled by DUSP2 at multiple levels including transcription, maturation, and extracellular vesicle-associated secretion. Our findings provide the proof of concept that blocking DUSP2/Exo-VEGF-C axis may serve as an attractive therapeutic approach to inhibit early dissemination of pancreatic cancer. Citation Format: Shaw-Jenq Tsai, Chu-An Wang, I-Heng Chang. Effect of DUSP2 on pancreatic cancer lymphatic dissemination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1786. |
| Databáze: | OpenAIRE |
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